The long term goal of this project is to develop a novel cone beam volume computed tomography breast imaging (CBVCTBI) technique to provide clinically useful three-dimensional (3D) high resolution tomographic images for breast cancer detection. CBVCTBI will require only a single fast volume scanning (4.8-9.6 seconds) to provide true 3D description of breast anatomy with 2.0-5.0 1p/mm isotropic resolution and will provide adequate low contrast resolution and high contrast spatial resolution for breast cancer detection.The clinical significance of CBVCTBI is that it will improve the sensitivity of breast cancer detection due to its much better low contrast resolution, compared to conventional mammography. CBVCTBI with high resolution volume of interest (VOI) reconstruction mode for target imaging, will also better characterize breast tumors three-dimensionally; conventional mammography does not provide 3D information of breast cancer. CBVCTBI will be developed and validated through computer simulation, phantom and specimen studies performed on a specially designed DBVCTBI prototype system that uses a flat panel detector (FPD) and cone beam tomographic acquisition geometry. This is an R21-R33 combined project. Specific aims of the R21project include: 1) Perform phantom studies to determine the required total exposure level (absorbed patient dose) for breast cancer imaging task, 2) Implement and optimize a fast cone beam reconstruction algorithm on a dual processor PC workstation, 3) Perform a comparison study of breast coverage near the chest wall between a conventional mammography system and a slightly modified standard stereotactic biopsy table (which will be used for the prototype CBVCTBI scanner) to provide evidence for appropriate coverage of the breast near the chest wall. 4) Obtain institutional review boar (IRB) approval to image breast specimens in the R33 project period. Specific aims for the R33 project period include: 1) Estimate glandular radiation dose for CBVCTBI technique, 2) Implement and optimize the cone beam reconstruction algorithms based on the different new volume scan schemes, 3) Develop the FPD-based prototype system, 4) Evaluate the prototype system, 5) Perform phantom and specimen studies to validate the CBVCTBI technique and optimize the system performance.